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genetics of schizophrenia

Posted by alexandra_k on September 26, 2006, at 20:45:15

> His plan was to make use of the extensive available genealogical and census data on the Icelandic population, the relative homogeneity of the Icelandic gene pool and the general willingness of the Icelandic population to participate in research projects. Having managed to raise venture capital to found the genomics company deCODE genetics, Inc., the deCODE CEO managed to establish an alliance in 1998 with the pharmaceutical company Hoffman-La Roche. Among key initial targets were genetic risk factors in 12 common complex disorders, including Schizophrenia and stroke.

> While deCODE's perhaps overzealous plans to establish a comprehensive national healthcare database linking encrypted demographic, clinical and genetic data of all Icelanders (29,000) has not materialised despite parlimentary support, the genomics company has been meeting its goals of identifying loci and genes for several complex brain disorders in the past 2 years. All participants in these studies have provided a signed informed consent form and all personal identifiers are encryped PIN codes provided by the Ieclandic Data Protection Authority. deCODE has also recently published a high-resolution map of the human genome. Over the past two years the company has been changing fast from a genomics company to a biotechnology company which aims to develop drugs faster than previously thought tenable through acquisitions and close collaboration with the pharmaceutical industry.

> Among the central elements of deCODE's successful approach has been the making of a new computerized genealogical database called Islendingabok - the Book of Icelanders. This database extends back to the settlers described in the Book of Settlements, but with greater reliability back to the complete census in 1703. The Book of Icelanders includes the names of about half of the Icelanders who have ever lived and of 95% of those born since the first complete census in 1703. No other biotechnology company has access to such a powerful tool to establish familiarity between participants, e.g., second and third cousins, in genetic research...

>'This core 7-marker haplotype was present in 7.6% of 394 controls and 14.4% of 402 independent affecteds, thereby conferring a relative risk of around 2.1 (p=0.000087)'

I'm not sure how they get from 7.6% of people without schizophrenia having the 7-marker haplotype and 14.4% of people with schizophrenia having the 7-marker haplotype to this:

>'On the basis of these frequencies and relative risks, the 7-marker haplotype has a population attributable risk of 16% under a multiplicative model, indicating that 16% of schizophrenia in Iceland could be eradicated if the haplotype were - in theory - eliminated from the Icelandic population (Stefansson et al., 2002)'

Do the findings generalise outside the Icelandic population (the Icelandic population is more homogenous than most)?

> 'Among Scots [who are historically similar to Icelanders] the 7-marker core haplotype was found in 10.2% of around 609 patients and 5.9% of 618 controls (p=0.00031) and conferred a relative risk of 1.8'

Findings have also been replicated in the UK, China, and Ireland (though the Scots result was the closest to the Icelandic result)


Journal of Mental Health, February 2004; 13(1): 21-27

(There is also an appendix where the author provides his login information so you can login to the Book of Icelanders project online)

 

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